[Paper Review] Cell damage and mitigation in Swiss albino mice: experiment and modelling

Urmimala Dey, Archismaan Ghosh+3 more|arXiv (Cornell University)|Apr 5, 2019

Immunotoxicology and immune responses16 references4 citations

TL;DR

This study investigates in vivo arsenic-induced cell damage in Swiss albino mice and its mitigation by black tea using experimental data and dynamical modeling. The results show black tea significantly reduces tumor cell damage progression and induces early saturation of damage, with a simple model accurately fitting the data and predicting long-term behavior.

ABSTRACT

Chronic exposure to inorganic arsenic is a potential cause of carcinogenesis. It elicits its potential by generation of ROS, leading to DNA, protein and lipid damage. Therefore, the deleterious effect of arsenic can be mitigated by quenching ROS using antioxidants. There is a homology between the protein coding regions of mice and human. Effect of these alterations in human can be mimicked in mice. Therefore to understand the underlying mechanism of arsenic toxicity and its amelioration by black tea, studies have been conducted in mice model. Long term exposure to iAs leads to tumour growth, which has been found to be alleviated by black tea. Observations reveal that black tea has two salutary effects on the growth of tumour: the rate of growth of damaged cells was appreciably reduced and an early saturation of the level of damage is achieved. To take the experimental findings further, the experimental data have been modelled with simple dynamical equations. The curves obtained from extit{in vivo} studies have been fitted with the data obtained from the model. The corresponding steady states and their stabilities are analyzed.

Motivation & Objective

• To understand the mechanisms of inorganic arsenic (iAs)-induced carcinogenesis and its mitigation by natural antioxidants.
• To evaluate the chemopreventive potential of black tea in reducing iAs-induced cell damage in a mouse model.
• To develop and validate a dynamical model that captures the progression of cell damage under iAs exposure and its alleviation by black tea.
• To analyze the stability of equilibrium states in the model to predict long-term tumor growth dynamics.

Proposed method

• Conducted long-term in vivo experiments with Swiss albino mice exposed to 500 µg/L iAs in drinking water for 360 days.
• Administered black tea extract (100 µg/ml) via gavage three times daily to a subset of mice to assess chemopreventive effects.
• Collected and analyzed blood and tissue samples at multiple time points to quantify cell damage over time.
• Fitted experimental data on cell damage progression to a system of nonlinear ordinary differential equations modeling damage dynamics.
• Analyzed steady states and their stability using mathematical analysis, including conditions for asymptotic stability.
• Used HPLC to quantify catechin and theaflavin content in tea extracts for dose standardization.

Experimental results

Research questions

• RQ1 How does chronic inorganic arsenic exposure affect cell damage progression in Swiss albino mice over time?
• RQ2 To what extent does black tea administration mitigate arsenic-induced cell damage in vivo?
• RQ3 Can a simple dynamical model accurately reproduce the experimental data on cell damage with and without black tea?
• RQ4 What are the stability properties of the model’s equilibrium states under iAs exposure and tea intervention?
• RQ5 Does the model predict early saturation of damage levels due to black tea, and what does this imply for tumor growth limitation?

Key findings

• Chronic iAs exposure led to progressive increase in cell damage, with damage levels not starting from zero due to pre-existing damage in control animals.
• Black tea administration significantly reduced the rate of cell damage progression and induced early saturation of damage levels.
• The experimental data for both iAs-only and iAs+black tea groups were well-fitted by the proposed dynamical model.
• Stability analysis revealed that the equilibrium state under black tea treatment is asymptotically stable under specific conditions involving parameters ε, n*, M*, L*, and P₂*.
• The model predicted long-term behavior of cell damage, suggesting that black tea could effectively limit tumor growth by stabilizing damage at lower levels.
• No significant toxicity was observed from black tea alone, supporting its safety as a chemopreventive agent in this model.